Expression of osteogenic protein-1 mRNA in cultured kidney cells

Osteogenic protein-1 (OP-1 or BMP-7) is a multifunctional cytokine that reg ulates the development of several tissues during embryogenesis, including t he skeleton, eye, and kidney. In postnatal life, OP-1 expression is most ab undant in the kidney, although the cellular localization of this expression has not been described. In this study, we utilized a cell culture approach to localize OP-1 mRNA expression in various renal cell types and to determ ine potential target cells for OP-1 effects. OP-1 mRNA expression was demon strated in several glomerular cell types, such as mesangial, epithelial, an d endothelial cells. Distal tubule MDCK cells also expressed OP-1 mRNA but human proximal tubule HK-2 cells did not. Multiple OP-1 transcripts, which ranged in size from 1.6 to 3.8 kb, were observed in both glomerular and tub ule cells. Interestingly, the pattern of expression varied among the differ ent cell types, suggesting cell-specific expression of OP-1 mRNA. Analysis of OP-1 receptor expression revealed transcripts for BMP receptors type IA and IB in HK-2 cells and transcripts for BMPR-IA and ALK-2 in mesangial cel ls. Treatment of HK-2 cells with OP-1 (300 ng/ml) for 24-48 hr increased ce llular proliferation whereas treatment of cells with transforming growth fa ctor-beta had no effect. Mesangial cell proliferation was not affected by O P-1. The results suggest that OP-1 is produced in the renal glomerulus and then travels to the proximal tubule to regulate the proliferation of cells in this region of the nephron. (C) 1999 Wiley-Liss, Inc.